Early ReportAnti-inflammatory cytokine profile and mortality in febrile patients
Introduction
We have suggested that an innate anti-inflammatory cytokine profile contributes to fatal meningococcal disease,1, 2 based on first-degree relatives of patients with fatal meningococcal disease having high ratios of the anti-inflammatory cytokine interleukin 10 (IL-10) to the proinflammatory cytokine tumour necrosis factor α (TNFα) after whole-blood stimulation in vitro. Studies in families, monozygotic twins, healthy individuals, and patients with sepsis have shown that the production of proinflammatory and anti-inflammatory cytokines is largely influenced by genetic factors.2, 3, 4 This finding raises the possibility that an innate cytokine profile after inflammatory insults substantially influences the outcome in infectious diseasēs.
Genetically-determined resistance and susceptibility of the host to infection with specific pathogens has received much attention and has been studied extensively in animal models.5, 6, 7 However, little is known about host factors in human beings, which on infection, direct the cytokine cascade in a proinflammatory or anti-inflammatory direction, and whether such factors substantially influence the outcome of disease.8 We investigated whether an anti-inflammatory cytokine profile is associated with an adverse outcome of infectious diseases. We measured plasma concentrations of IL-10 and TNFα in patients who presented to hospital with fever, in early and advanced stages of systemic inflammatory reaction.
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Patients and methods
We did this study at the Leiden University Hospital, an 800-bed secondary and tertiary referral centre. We included over an 18-month period 464 patients aged older than 18 years consecutively admitted to the accident and emergency department because of community-acquired febrile illness (rectal temperature ≥38·2°C). Another 16 patients were enrolled but were excluded because they did not meet the inclusion criteria, adequate data could not be collected, or because they were lost to follow-up.
We
Results
We included 272 men and 192 women. The median age was 61 years (range 18–97). About 70% of the patients were referred to the hospital by their family physician, 18% by another physician, and the rest were self-referred. 61 (13·1%) patients had received oral antibiotic treatment in the week before admission, whereas 65 (14·0%) had received some kind of therapy that may have been immunosuppressive, such as low-dose oral prednisone for chronic obstructive pulmonary disease.
On admission, 332
Discussion
The anti-inflammatory cytokine profile associated with mortality that we identified is characterised by a high ratio of IL-10 to TNFα. These data extend to community-acquired infections our previous findings that an anti-inflammatory cytokine profile is an innate host characteristic that contributes to fatal meningococcal disease.1, 2
In at least 85% of the cases in this study, the fever on hospital admission was definitely caused by an infection in the respiratory or urinary tract. The patients
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2020, Critical Care Clinics